UniProt functional annotation for Q9Y5A9



	UniProt functional annotation for Q9Y5A9

UniProt code: Q9Y5A9.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Specifically recognizes and binds N6-methyladenosine (m6A)- containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:32492408, PubMed:25412658, PubMed:25412661). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054, PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:32492408). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A- containing mRNAs (PubMed:27558897). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315). Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (By similarity). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation (PubMed:32169943). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (PubMed:30428350). Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation (PubMed:30559377). May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (PubMed:32267835). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31388144, PubMed:31292544, PubMed:32451507, PubMed:31642031). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (PubMed:31815440). {ECO:0000250|UniProtKB:Q91YT7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25412658, ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:26046440, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:30065315, ECO:0000269|PubMed:30428350, ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:30930054, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:31642031, ECO:0000269|PubMed:31815440, ECO:0000269|PubMed:32169943, ECO:0000269|PubMed:32267835, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.

Function: (Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282). {ECO:0000269|PubMed:29447282}.

Function: (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)- containing viral RNAs (PubMed:29659627). {ECO:0000269|PubMed:29659627}.

Subunit: Interacts with CNOT1; interaction is direct and promotes recruitment of the CCR4-NOT complex (PubMed:27558897, PubMed:32492408). Interacts with YTHDF3 (PubMed:28106072). Interacts with RIDA/HRSP12; interaction leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). {ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:30930054, ECO:0000269|PubMed:32492408}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:32492408}. Cytoplasm, P-body {ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:32492408}. Cytoplasm, Stress granule {ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:32451507}. Nucleus {ECO:0000269|PubMed:26458103}. Note=Localizes to the cytosol and relocates to the nucleus following heat shock stress (PubMed:26458103). Can partition into different structures: into P-bodies in unstressed cells, and into stress granules during stress (PubMed:31292544). {ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:31292544}.

Tissue specificity: Highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation. {ECO:0000269|PubMed:32169943}.

Induction: Following heat shock stress. {ECO:0000269|PubMed:26458103}.

Domain: The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues (PubMed:31292544). This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons (PubMed:31292544). {ECO:0000269|PubMed:31292544}.

Ptm: Ubiquitinated by the SCF(SKP2) complex, leading to its degradation. {ECO:0000269|PubMed:32267835}.

Similarity: Belongs to the YTHDF family. YTHDF2 subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAD42861.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAF08813.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAL99921.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Specifically recognizes and binds N6-methyladenosine (m6A)- containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:32492408, PubMed:25412658, PubMed:25412661). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054, PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:32492408). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A- containing mRNAs (PubMed:27558897). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315). Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (By similarity). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation (PubMed:32169943). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (PubMed:30428350). Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation (PubMed:30559377). May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (PubMed:32267835). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31388144, PubMed:31292544, PubMed:32451507, PubMed:31642031). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (PubMed:31815440). {ECO:0000250\|UniProtKB:Q91YT7, ECO:0000269\|PubMed:22575960, ECO:0000269\|PubMed:24284625, ECO:0000269\|PubMed:25412658, ECO:0000269\|PubMed:25412661, ECO:0000269\|PubMed:26046440, ECO:0000269\|PubMed:26318451, ECO:0000269\|PubMed:26458103, ECO:0000269\|PubMed:27558897, ECO:0000269\|PubMed:28106072, ECO:0000269\|PubMed:30065315, ECO:0000269\|PubMed:30428350, ECO:0000269\|PubMed:30559377, ECO:0000269\|PubMed:30930054, ECO:0000269\|PubMed:31292544, ECO:0000269\|PubMed:31388144, ECO:0000269\|PubMed:31642031, ECO:0000269\|PubMed:31815440, ECO:0000269\|PubMed:32169943, ECO:0000269\|PubMed:32267835, ECO:0000269\|PubMed:32451507, ECO:0000269\|PubMed:32492408}.



Function:		(Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282). {ECO:0000269\|PubMed:29447282}.



Function:		(Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)- containing viral RNAs (PubMed:29659627). {ECO:0000269\|PubMed:29659627}.


Subunit:		Interacts with CNOT1; interaction is direct and promotes recruitment of the CCR4-NOT complex (PubMed:27558897, PubMed:32492408). Interacts with YTHDF3 (PubMed:28106072). Interacts with RIDA/HRSP12; interaction leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). {ECO:0000269\|PubMed:27558897, ECO:0000269\|PubMed:28106072, ECO:0000269\|PubMed:30930054, ECO:0000269\|PubMed:32492408}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:26458103, ECO:0000269\|PubMed:31292544, ECO:0000269\|PubMed:32492408}. Cytoplasm, P-body {ECO:0000269\|PubMed:24284625, ECO:0000269\|PubMed:31292544, ECO:0000269\|PubMed:32492408}. Cytoplasm, Stress granule {ECO:0000269\|PubMed:31292544, ECO:0000269\|PubMed:32451507}. Nucleus {ECO:0000269\|PubMed:26458103}. Note=Localizes to the cytosol and relocates to the nucleus following heat shock stress (PubMed:26458103). Can partition into different structures: into P-bodies in unstressed cells, and into stress granules during stress (PubMed:31292544). {ECO:0000269\|PubMed:26458103, ECO:0000269\|PubMed:31292544}.
Tissue specificity:		Highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation. {ECO:0000269\|PubMed:32169943}.
Induction:		Following heat shock stress. {ECO:0000269\|PubMed:26458103}.
Domain:		The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues (PubMed:31292544). This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons (PubMed:31292544). {ECO:0000269\|PubMed:31292544}.
Ptm:		Ubiquitinated by the SCF(SKP2) complex, leading to its degradation. {ECO:0000269\|PubMed:32267835}.
Similarity:		Belongs to the YTHDF family. YTHDF2 subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAD42861.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAF08813.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAL99921.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};